Arginine vasopressin controls p27(KiP1) protein expression by PKC activation and irreversibly inhibits the proliferation of K-Ras-dependent mouse Y1 adrenocortical malignant cells

The neurohypophyseal hormone arginine vasopressin (AVP) is a classic mitogen in many cells. In K-Ras-dependent mouse Y1 adrenocortical malignant cells, AVP elicits antagonistic responses such as the activation of the PKC and the ERK1/2 mitogenic pathways to down-regulate cyclin D1 gene expression, which induces senescence-associated beta-galactosidase (SA-beta Gal) and leads to cell cycle arrest. Here, we report that in the metabolic background of Y1 cells, PKC activation either by AVP or by PMA inhibits the PI3K/Akt pathway and stabilises the p27(Kip1) protein even in the presence of the mitogen fibroblast growth factor 2 (FGF2). These results suggest that p27(Kip1) is a critical signalling node in the mechanisms underlying the survival of the Y1 cells. In Y1 cells that transiently express wild-type p27(Kip1), AVP caused a severe reduction in cell survival, as shown by clonogenic assays. However, AVP promoted the survival of Y1 cells transiently expressing mutant p27-S10A or mutant p27-T187A, which cannot be phosphorylated at Ser10 and Thr187, respectively. In addition, PKC activation by PMA mimics the toxic effect caused by AVP in Y1 cells, and inhibition of PKC completely abolishes the effects caused by both PMA and AVP in clonogenic assays. The vulnerability of Y1 cells during PKC activation is a phenotype conditioned upon K-ras oncogene amplification because K-Ras down-regulation with an inducible form of the dominant-negative mutant H-RasN17 has resulted in Y1 cells that are resistant to AVP`s deleterious effects. These data show that the survival destabilisation of K-Ras-dependent Y1 malignant cells by AVP requires large quantities of the p27(Kip1) protein as well as phosphorylation of the p27(Kip1) protein at both Ser10 and Thr187. (C) 2011 Elsevier B.V. All rights reserved.

Mutagenicity and DNA adduct formation of PAH, nitro-PAH, and oxy-PAH fractions of atmospheric particulate matter from Sao Paulo, Brazil

Urban particulate matter (UPM) contributes to lung cancer incidence. Here, we have studied the mutagenic activity and DNA adduct-forming ability of fractionated UPM extractable organic matter (EOM). UPM was collected with a high-volume sampler in June 2004 at two sites, one at street level adjacent to a roadway and the other inside a park within the urban area of the city of Sao Paulo, Brazil. UPM was extracted using dichloromethane, and the resulting EOM was separated by HPLC to obtain PAH, nitro-PAH, and oxy-PAH fractions which were tested for mutagenicity with the Salmonella strains TA98 and YG1041 with and without S9 metabolic activation. The PAH fraction from both sites showed negligible mutagenic activity in both strains. The highest mutagenic activity was found for the nitro-PAH fraction using YG1041 without metabolic activation; however, results were comparable for both sites. The nitro-PAH and oxy-PAH fractions were incubated with calf thymus DNA under reductive conditions appropriate for the activation of nitro aromatic compounds, then DNA adduct patterns and levels were determined with thin-layer chromatography (TLC) (32)p-postlabeling method using two enrichment procedures-nuclease PI digestion and butanol extraction. Reductively activated fractions from both sites produced diagonal radioactive zones (DRZ) of putative aromatic DNA adducts on thin layer plates with both enrichment procedures. No such DRZ were observed in control experiments using fractions from unexposed filters or from incubations without activating system. Total adduct levels produced by the nitro-PAH fractions were similar for both sites ranging from 30 to 45 adducts per 10(8) normal nucleotides. In contrast, the DNA binding of reductively activated oxy-PAH fractions was three times higher and the adduct pattern consisted of multiple discrete spots along the diagonal line on the thin layer plates. However, DNA adduct levels were not significantly different between the sampling sites. Both samples presented the same levels of mutagenic activity. The response in the Salmonella assay was typical of nitroaromatics. Although, more mutagenic activity was related to the nitro-PAH fraction in the Salmonella assay, the oxy-PAH fractions showed the highest DNA adduct levels. More studies are needed to elucidate the nature of the genotoxicants occurring in Sao Paulo atmospheric samples. (C) 2008 Elsevier B.V. All rights reserved.

Att vara anhörigvårdare till en lungcancersjuk patient

Syftet med denna systematiska litteraturstudie är att undersöka upplevelser hos anhörigvårdare till lungcancerpatienter. Artikelsökningar har skett i Cinahl och Pubmed. Tiden för anhörigvårdaren kan se olika ut, kort och intensiv eller lång och utmattande. Upplevelser så som skräck är vanligt förekommande direkt efter lungcancerdiagnosen både för patient och vårdare. Detta för att de anhöriga ställs inför ett klart hot om en kommande förlust samt skrämmande tankar kring döden. Hälsan försämras för anhörigvårdaren under vårdtiden och vissa drabbas av depression. De social relationerna försämras, vissa upphör helt då anhörigvårdaren får en känsla av att de alltid måste vara tillgängliga för den sjuke. Vårdbördan kan vara tung och emotionellt stöd kan vara nödvändigt. Trots det väljer många att inte ta emot eller söka något stöd.Inte bara hälsan förändras under sjukdomstiden utan också mycket annat, den som tidigare haft en passiv roll i hushållet kan bli tvungen att ta en mer aktiv roll i skötseln av hem och ekonomi. Trots att anhörigvårdare ofta känner sig utanför och övergivna väljer de att inte uttrycka sina känslor när de blir tillfrågade eftersom det finns en rädsla att ta fokus från patienten.

Upplevelser av lungcancervården: Patient och närståendes perspektiv : En empirisk studie med kvalitativ ansats

Syfte: Syftet var att utifrån patienters och närståendes nerskrivna berättelser ta del av deras upplevelser och erfarenheter av lungcancervården samt att utifrån dessa berättelser identifiera förbättringsidéer.Metod: Studien hade en empirisk design med kvalitativ ansats. Datainsamlingen skedde via idéböcker. Materialet analyserades genom kvalitativ innehållsanalys.Resultat: Två teman framkom i resultat. Det första temat var: Känslor av otrygghet och lidande kopplat till vården, livet och den egna sjukdomen. De tillhörande kategorierna var vårdlidande, livslidande och sjukdomslidande. Det andra temat var: Känslor av trygghet kopplat till goda mellanmänskliga relationer. Tillhörande kategori var goda mellanmänskliga relationer. Utökat psykosocialt stöd och utbildning i kommunikation till personal fanns bland de idéer för utveckling av lungcancervården som framkom.Konklusion: Denna studie visade att patienter med lungcancer kände otrygghet och lidande, till stor del orsakat av vården. Där goda möten ägde rum skapades trygghet och goda mellanmänskliga relationer. Utökat psykosocialt stöd och utbildning i kommunikation till personal fanns bland de idéer för utveckling av lungcancervården som framkom.

Sjuksköterskans främjande av livskvalitet hos lungcancerpatienter i palliativ fas : En litteraturöversikt

Bakgrund: Lungcancer är en sjukdom med dålig prognos och hög dödlighet. Många patienter behandlas därför med palliativ vård. Att ha lungcancer påverkar patientens livskvalitet, och sjuksköterskan har ett stort ansvar i att främja patientens livkvalitet. Syfte: Att beskriva vad som innefattades i begreppet livskvalitet utifrån lungcancersjuka patienter i palliativ fas, vilka faktorer som påverkade känslan av den och hur sjuksköterskan kunde främja livskvalitet utifrån sin yrkesroll. Metod: Studien genomfördes som en litteraturöversikt. Totalt användes 25 artiklar av både kvalitativ och kvantitativ ansats. Artiklar till studien söktes i databaserna CINHAL och PubMed. Resultat: Livskvalitet är ett multidimensionellt begrepp och det kan ses som någonting individuellt och unikt för varje enskild lungcancersjuk patient, och innebörden av begreppet hade olika betydelse för alla. Livskvalitet kunde påverkas utifrån både fysiska, psykiska, sociala och existentiella aspekter. Sjuksköterskan hade därför en viktig roll i att ha en helhetssyn på patienten och se denne som en enskild individ i situationen, för att livskvalitet ska kunna främjas optimalt hos patienten. Slutsats: Livskvalitet är ett oändligt begrepp, som har en unik betydelse för varje patient. Som sjuksköterska fanns inget facit på vilka åtgärder som bäst kan främja patientens livskvalitet. Dock handlar det om till stor del för sjuksköterskan att våga möta patienten i denna svåra situation och att våga lyssna på patienten.

Hälsa och livskvalitet hos personer diagnostiserade med lungcancer : En deskriptiv enkätstudie

Syfte: Syftet med studien var att undersöka skattningen av hälsa och livskvalitet utifrån kön, ålder och rökvanor hos personer med lungcancer. Vidare syftade studien till att undersöka om det fanns samband mellan specifika sjukdomssymptom och personens skattning av hälsa, livskvalitet och förekomsten av rökning eller tidigare rökning. Metod: Studien genomfördes som en deskriptiv studie. Deltagarna (n=68) var samtliga diagnostiserade med lungcancer och bosatta i Dalarna, Sverige. Resultat: Ökade besvär av vissa sjukdomssymptom, däribland svårigheter att ta en långpromenad samt trötthet, hade ett signifikant samband med en lägre skattad hälsa. Vid ökade besvär av vissa sjukdomssymptom, däribland nedstämdhet och sömnsvårigheter, sågs samband med en lägre skattning av livskvaliteten. Personer som var, eller tidigare hade varit rökare, hade i högre utsträckning besvär av vissa sjukdomssymptom som andfåddhet och svårigheter att göra ansträngande saker. Sammanfattning: Studien visade att det fanns signifikanta samband mellan vissa sjukdomssymptom och hur personen med lungcancer upplever sin hälsa och livskvalitet. Detta är viktigt att bejaka i omvårdnaden av personer som drabbats för att kunna främja hälsa och livskvalitet. Det fanns även signifikanta samband mellan vissa sjukdomssymptom och förekomsten av rökning eller tidigare rökning. Detta är en indikation på att hälso- och sjukvården bör fortsätta att arbeta tobakspreventivt för att motiverat att arbeta för att personer ska sluta röka.

Cathepsin S as a biomarker of low-grade inflammation, insulin resistance, and cardiometabolic disease risk

Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.    The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.    This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.    In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.    Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations. 

Mortalidade por câncer de boca e condição sócio-econômica no Brasil

BORGES,D. M. L.et al. Mortalidade por câncer de boca e condição sócio-econômica no Brasil.Cad. Saúde Pública, Rio de Janeiro, v.25,n.2, p.321-327, fev, 2009

Câncer de boca e orofaringe: tendências e análise de sobrevida em Natal (RN)

Introduction: Mouth cancer is classified as having one of the ten highest cancer incidences in the world. In Brazil, the incidence and mortality rates of oral cancer are among the highest in the world. Intraoral cancer (tongue, gum, floor of the mouth, and other non-specified parts of the mouth), the accumulated survival rate after five years is less than 50%. Objectives: Estimate the accumulated survival probability after five years and adjust the Cox regression model for mouth and oropharyngeal cancers, according to age range, sex, morphology, and location, for the city of Natal. Describe the mortality and incidence coefficients of oral and oropharyngeal cancer and their tendencies in the city of Natal, between 1980 and 2001 and between 1997 and 2001, respectively. Methods: Survival data of patients registered between 1997 and 2001 was obtained from the Population-based Cancer Record of Natal. Differences between the survival curves were tested using the log-rank test. The Cox proportional risk model was used to estimate risk ratios. The simple linear regression model was used for tendency analyses of the mortality and incidence coefficients. Results: The probability after five years was 22.9%. The patients with undifferentiated malignant neoplasia were 4.7 times more at risk of dying than those with epidermoid carcinoma, whereas the patients with oropharyngeal cancer had 2.0 times more at risk of dying than those with mouth cancer. The mouth cancer mortality and incidence coefficients for Natal were 4.3 and 2.9 per 100 000 inhabitants, respectively. The oropharyngeal cancer mortality and incidence coefficients were, respectively, 1.1 and 0.7 per 100 000 87 inhabitants. Conclusions: A low survival rate after five years was identified. Patients with oropharyngeal cancer had a greater risk of dying, independent of the factors considered in this study. Also independent of other factors, undifferentiated malignant neoplasia posed a greater risk of death. The magnitudes of the incidence coefficients found are not considered elevated, whereas the magnitudes of the mortality coefficients are high

Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Câncer de pulmão: histologia, estádio, tratamento e sobrevida

OBJETIVO: Analisar os principais tipos histológicos, estádio, tratamento e sobrevida dos portadores de câncer de pulmão. MÉTODOS: Estudo retrospectivo a partir da análise dos prontuários de pacientes acompanhados no Hospital das Clínicas da Faculdade de Medicina de Botucatu, num período de seis anos. RESULTADOS: de janeiro de 2000 a janeiro de 2006, foram acompanhados 240 doentes com câncer de pulmão, com predominância do sexo masculino (64%). O tipo histológico mais freqüente foi o carcinoma escamoso (37,5%), seguido pelo adenocarcinoma (30%), carcinoma neuroendócrino (19,6%) e carcinoma de grandes células (6,6%). Apenas 131 pacientes (54,6%) foram tratados. Destes, 52 pacientes (39,7%) foram submetidos à quimioterapia exclusiva, 32 (24,4%) realizaram quimioterapia associada à radioterapia e 47 (35,9%) foram submetidos à cirurgia associada ou não à quimioterapia exclusiva e/ou radioterapia. Somente 27 pacientes (20,6%) foram submetidos à cirurgia exclusiva.Em relação ao estadiamento, 34,4% apresentavam, no momento do diagnóstico, estádio IV, 20,6% estádio IIIB, 16,8% estádio IIIA e os outros 28,2% pertenciam aos estádios I e II. A sobrevida em cinco anos foi de 65% para o estádio I e 25% para os estádios remanescentes. CONCLUSÕES: O tipo histológico predominante foi o carcinoma escamoso e o de menor freqüência foi o carcinoma de grandes células. A maioria se encontrava em estádio avançado ao diagnóstico, estando nos estádios iniciais menos de 30% dos casos. Isto justifica a baixa sobrevida e a pequena quantidade de pacientes submetidos ao tratamento cirúrgico exclusivo, em comparação à maioria que foi submetida à quimioterapia exclusiva.

Fatores associados a não realização da mamografia e do exame clínico das mamas: um estudo de base populacional em Campinas, São Paulo, Brasil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Trabalho industrial e câncer de pulmão

Com base em populações hospitalares, foram entrevistados 316 casos e 536 controles para obtenção de informações sobre histórias de trabalho, tabagismo, tabagismo passivo, ocorrência de outros cânceres na família, migração e situação socioeconômica. Os entrevistadores utilizaram um questionário padronizado. Casos e controles foram emparelhados por hospital, sexo e idade. O estudo foi desenvolvido entre 1º de julho de 1990 e 31 de janeiro de 1991 em 14 hospitais da Região Metropolitana de São Paulo, SP (Brasil). Foi elaborada uma classificação por escores como forma de ordenar os indivíduos estudados segundo suas histórias de exposições ocupacionais a cancerígenos, conhecidos para o pulmão, acumulando informações sobre a exposição nos locais de trabalho durante a vida, considerando o tipo de atividade, setor de trabalho e tempo em cada emprego. A análise de regressão logística não-condicional mostrou odds ratio: 1,97 (95% IC: 1,52 a 2,55) para os trabalhadores com maiores escores de exposição. Os resultados permitiram inferir que trabalhadores ligados aos setores de produção de diferentes ramos industriais têm duas vezes o risco de desenvolverem neoplasia pulmonar quando comparados aos trabalhadores envolvidos em atividades não-industriais.

Indoor radon measurements and methodologies in Latin American countries

According to the current international guidelines concerning environmental problems, it is necessary to evaluate and to know the indoor radon levels, specially since most of the natural radiation dose to man comes from radon gas and its progeny. Several countries have established National Institutions and National Programs for the study of radon and its connection with lung cancer risk and public health. The aim of this work is to present the indoor radon measurements and the detection methods used for different regions of Latin America (LA) in countries such as Argentina, Brazil, Ecuador, Mexico, Peru and Venezuela. This study shows that the passive radon devices based on alpha particle nuclear track methodology (NTM) is one of the more generalized methods in LA for long term indoor radon measurements, CR-39, LR-115 and Makrofol being the more commonly used detector materials. The participating institutions and the radon level measurements in the different countries are presented in this contribution. (C) 2001 Elsevier B.V. Ltd. All rights reserved.

Indoor radon measurements in six Latin American countries

Most of the natural radiation dose to man comes from radon gas and its progeny. Several countries have established national institutions and national programs in charge of the study of radon and its connection with lung cancer risk and public health. In this paper an indoor radon measurements in Latin American countries is presented. The participants in this work were from Argentina, Brazil, Ecuador, Mexico, Peru and Venezuela. Many different techniques are used in this common effort, and the indoor radon levels in specific locations in each of the participant countries are presented.